Programmed cell death-1 (PD-1) variants and circulating levels of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 levels with HBV infection and disease progression.
The study cohort consists of HBV-infected adults (n=513) stratified by clinical course, including chronic hepatitis B (CHB, n=173), liver cirrhosis (LC, n=134), hepatocellular carcinoma (HCC, n=206), and matched healthy controls (HC, n=196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and plasma sPD-1 levels were quantified by enzyme immunoassay.
The plasma sPD-1 levels were significantly high among HBV patients. The highest plasma sPD-1 levels were observed in CHB patients, followed by the LC and HCC groups. In addition, the plasma sPD-1 levels correlated positively with liver inflammation (aspartate transaminase, AST: rho=0.57, P<0.0001 and alanine aminotransferase, ALT: rho=0.57, P<0.0001) and were positively correlated with liver fibrosis (AST to Platelet Ratio Index, APRI score: rho=0.53, P<0.0001). The PD-1.9 TT genotype was less frequent in CHB patients compared to LC, HCC and HCC+LC patients in both codominant and recessive models (P<0.01) and was found to be a risk factor for HCC predisposition [HCC vs. non-HCC: OR=2.0 (95% CI: 1.13-3.7), P=0.017]. The PD-1.5 CT genotype was associated with a reduced risk of acquiring HCC [OR=0.6 (95%CI: 0.4-0.9), P=0.031].
Our study concludes that sPD-1 levels are associated with liver inflammation and progression of liver fibrosis and the PD-1.5 and PD-1.9 variants are associated with HBV infection and progression of liver disease.

Copyright © 2021. Published by Elsevier Ltd.